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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tizanidine [5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole] is able to increase the pain threshold in the tail-flick test in mice. The effect of tizanidine was investigated after treatment of mice with drugs influencing central monoaminergic and GABAergic mechanisms. A drug that inhibits the synthesis and storage of monoamines and drugs that cause specific lesions of monoaminergic neurons had no consistent effect on the antinociceptive action of tizanidine. The action of tizanidine was antagonized by the alpha 2-adrenoreceptor antagonist, yohimbine, but not by the alpha 1 antagonist prazosin, nor by dopamine, serotonin and GABA receptor antagonists. These results indicate that the antinociceptive action induced by tizanidine may be mediated by alpha 2-adrenoreceptors.
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PMID:Antinociceptive activity induced by tizanidine and alpha 2-adrenoreceptors. 282 57

In rats anaesthetised with alphaxalone/alphadolone (Saffan), bilateral microinjections of the GABA antagonist, bicuculline, into a restricted region of nucleus paragigantocellularis lateralis (PGL), ventromedial to the caudal pole of the facial nucleus, produced an increase in the latency of the tail flick response to noxious heat. The analgesia was always accompanied by a rise in mean arterial blood pressure but the time course of the cardiovascular and antinociceptive changes was different. Guanethidine (7 mg/kg i.v.) blocked the pressor response but had no effect on the magnitude or time course of the analgesia. In contrast, microinjection of physostigmine into PGL produced a pressor response but no change in the latency of the tail flick response. It is concluded that there are functionally distinct pools of neurones within PGL which respectively produce antinociception and changes in vasomotor activity. Ongoing activity in both types of neurone is regulated by a tonic inhibitory GABAergic influence. In addition, the cardiovascular neurones receive a tonic excitatory cholinergic input.
Pain 1987 Dec
PMID:Tonic GABAergic and cholinergic influences on pain control and cardiovascular control neurones in nucleus paragigantocellularis lateralis in the rat. 282 91

The peripheral control of appetite is effected by two digestive hormones produced by the stomach and intestine. Bombesin, induced by gastric distension, might act as a messenger informing the nervous centres that the subject is satiated. The pharmacological satiating effect of cholecystokinin, probably mediated by the afferent fibres of the vagus nerve, is well established, but its physiological effect has not yet been demonstrated. Centrally, appetite is controlled by neurotransmitters, satiating and orexigenic properties being shared between monoamines, benzodiazepine-receptors and GABA-receptors. Among digestive hormones present in the central nervous system, the most satiating in pharmacological doses seem to be cholecystokinin and calcitonin, but their physiological role remains obscure. Insulin might be the signal informing the hypothalamus on body fat mass. Endorphins exert an orexigenic effect, reversed by naloxone, which is particularly marked in case of stress, in obese subjects and in the presence of highly palatable food. The control of appetite therefore is complex. It cannot be separated from other functions, such as pain and pleasure, which are regulated by intracerebral peptides.
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PMID:[Mechanisms of the control of appetite]. 286 55

The experiments were carried out on Wistar rats, using a conflict situation consisting in opposition of two motivations: positive (water drinking) and negative (electrical pain). Two newly-synthesized piperazine derivatives with proved psychotropic activity (4P-183 and GP4) were studied and compared with the classical benzodiazepine tranquilizing agent diazepam. Parallel with this, the affinity of these compounds to the benzodiazepine receptor in mouse brain was tested (radioligand binding of 3H-diazepam), as well as the changes in the characteristics of binding (dissociation constant and density of the receptors) after 14-day administration o doses equal to 1/3 LD50 of the two compounds. The results indicate the existence of anxiolytic (anticonflict) activity in both compounds. The fact that the above-mentioned derivatives do not interact with 3H-diazepam (in vitro), changing above all the dissociation constant after chronic administration, suggests predominantly nonspecific type of binding to the receptors. It is possible that their anxiolytic activity is associated with indirect interactions with one of the components of the GABA-benzodiazepine receptor complex, similar to the atypical tranquillizers.
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PMID:Behavioural and radioligand analysis of the effect of two new piperazine derivatives with anxiolytic properties. 289 28

Against the background of the action of piracetam--a cyclic derivative of GABA--in a dose of 200-400 mg/kg, no significant changes were observed of probabilities of motor reactions to inhibitory and reinforced light flashes. Piracetam in that dose did not affect inhibitory pauses in responses of neurones in the visual area and corresponding late components of the evoked potential to nonreinforced light flashes, i.e. it did not intensify inhibitory hyperpolarization processes in the cerebral cortex. Piracetam administration improved differentiation of inhibitory and reinforced light flashes judging by bioelectric parameters of the brain activity as a result of intensification of pain reinforcement action on cortical neurones. The carried-out experiments revealed significant differences in neurophysiological mechanisms of action of piracetam and fenibut--GABA linear derivate related to nootropic class.
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PMID:[Effect of piracetam on the neuronal activity of the neocortex and on behavior in rabbits during learning]. 318 41

Neurotropin, an extract from the inflamed skin of vaccinia virus-inoculated rabbits, has been observed clinically to be effective for treating pain in patients with lumbago, SMON and other neuropathies. In the present study, we examined the mechanism of the antinociceptive effect of neurotropin in mice in relation to administration routes, opioids, and noradrenergic or GABAergic drugs, by the tail pressure method. The antinociceptive effects of neurotropin were large when administered by the i.p. and intracisternal (i.cist.) routes, but comparatively small in the case of the intrathecal (i.th.) route. Neurotropin may thus act at the supraspinal level rather than on the spinal cord. The antinociceptive effect of neurotropin was not blocked by naloxone, and no cross-tolerance developed between neurotropin and morphine. The effect of neurotropin was blocked by phentolamine and reserpine, but not by atropine. Its effect was enhanced by GABA, muscimol, aminooxyacetic acid and diaminobutyric acid, but not by baclofen, and blocked by bicuculline methiodide. From these results, the antinociceptive action of neurotropin appears to be non-opioid in nature, and may possible be mediated by the noradrenergic and GABAergic systems, but unrelated to the cholinergic system.
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PMID:Mechanism of the analgesic effect of neurotropin. 321 Apr 43

The onset of therapeutic effectiveness of carbamazepine is generally very rapid in the treatment of seizure and paroxysmal pain disorders, shows some lag in the treatment of mania, and exhibits the longest lag in depression. These time course variations may indicate that different mechanisms underlie the efficacy of carbamazepine in the differential neuropsychiatric syndromes. Biochemical and pharmacological data suggest that the anticonvulsant effects of carbamazepine are related to "peripheral-type" benzodiazepine and alpha 2-noradrenergic receptor systems and to its ability to stabilize sodium channels. GABAB (baclofen-like) actions appear to be involved in antinociceptive, but not anticonvulsant, effects. The relatively acute time course of antimanic efficacy may be related to the above-mentioned mechanisms or to other effects related to systems postulated to be altered in the manic syndrome. These effects might include carbamazepine's ability to increase acetylcholine in the striatum, decrease probenecid-induced levels of CSF homovanillic acid (HVA) in man and dopamine turnover in animals, decrease CSF norepinephrine in manic patients, inhibit adenylate cyclase activity (in response to norepinephrine, dopamine, adenosine, or ouabain), decrease GABA turnover, or act as a vasopressin agonist. Efficacy in depression may be related to actions in man that take time or chronic drug administration to develop, such as increases in plasma tryptophan, decreases in CSF somatostatin, decreases in thyroid indices, and increases in urinary free cortisol excretion and, in animals, increases in substance P sensitivity and increases in brain adenosine receptors. The ability of carbamazepine to block the development of lidocaine- and cocaine-induced seizures also requires chronic administration, suggesting that these seizure models may provide a unique perspective for understanding mechanisms of time-dependent effects.
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PMID:Time course of clinical effects of carbamazepine: implications for mechanisms of action. 328 May 60

The possibility that GABAergic neurons in the ventral periaqueductal gray matter modulate the analgesic effects of morphine microinjected into this brain area was investigated in the rat. Microinjection of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin 3-ol (THIP) (0.4 microgram in 0.2 microliter), a GABA agonist, in the ventral periaqueductal gray matter significantly reversed the increase of tail-flick latency induced by a prior injection of morphine sulfate (4 micrograms in 0.2 microliter) at the same site. Conversely, microinjection in the same region of picrotoxin (10 ng in 0.2 microliter), a GABA antagonist, significantly potentiated the analgesic effect of the same dose of morphine. These results suggest the existence of GABAergic neurons that tonically inhibit periaqueductal gray output neurons involved in centrifugal pain inhibition. The analgesic effects of opiates may, at least in part, result from disinhibition of these GABAergic neurons.
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PMID:GABAergic modulation of the analgesic effects of morphine microinjected in the ventral periaqueductal gray matter of the rat. 343 24

Spectrum of the analgetic activity of GABA derivatives baclofen (2.5-10.0 mg/kg) and tolibut (12.5-100.0 mg/kg) was studied in experiments on albino mice and rats. Baclofen and especially tolibut showed a dose-dependent inhibition of perceptive, emotional and autonomic manifestations of nociceptive reactions at the tail's thermal and electrical stimulation and enhancement of the analgetic effect of promedol. The regressive analysis made it possible to show dependence of the analgetic effect on the level of pain sensitivity and emotional reactivity of the animals. Tolibut deepens and prolongs sombrevin anesthesia, baclofen fails to alter it.
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PMID:[The spectrum of analgesic activity of baclofen and tolibut]. 355 47

The above results with intracerebral drug injection and electrical brain stimulation in rats indicate that enhancement of GABAergic activity in the dorsal CG or in the MH raises the threshold of electrical stimulation inducing aversive behavior when applied to these brain areas. Conversely, drug-induced reduction of GABA action in the dorsal CG or in the MH leads to aversive-like behavioral changes. Therefore, GABAergic fibers seem to exert tonic inhibition on neuronal groups in the CG and MH integrating aversive behavioral states. Anxiolytics may cause anti-aversive effects by enhancing this GABAergic modulation. As discussed elsewhere, serotonergic and opioid mechanisms are also likely to operate in periventricular brain areas. In conjunction with GABAergic mechanisms, they may be involved in the pathophysiology of anxiety, panic attacks and pain, as well as in the therapeutic action of anxiolytics, anti-panic drugs and centrally-acting analgesics.
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PMID:Role of GABA in the anti-aversive action of anxiolytics. 376 23


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